Work

Deciphering the integrated immunogenomic landscape of colorectal cancer: insights from Mendelian randomization and immune-stratified molecular subtyping

Year: 2025

Type: article

Abstract: PURPOSE: This study aimed to decipher the intricate interplay between the immune landscape and CRC pathogenesis, elucidating how distinct immunophenotypes causally influence disease susceptibility and stratify patient outcomes. METHODS: We obtained the immunocyte phenotypes and CRC data from their respective genome-wide association studies. The primary analysis used the inverse variance weighting (IVW) method. We also simultaneously employed MR-Egger, weighted mode, simple mode, and weighted median approaches to strengthen the findings. Consensus clustering stratified 619 TCGA CRC patients by immunome expression. Functional assays examined the tumor suppressor GPD1L. RESULTS: The IVW MR analysis identified 17 immunocyte phenotypes positively potentially associated with increased CRC risk (P < 0.05, OR > 1), and 18 phenotypes negatively potentially associated with decreased CRC risk (P < 0.05, OR < 1). These associations were not confounded by heterogeneity or horizontal pleiotropy (P > 0.05). Reverse MR analysis further revealed 4 additional immunocyte phenotypes positively potentially associated with CRC (P < 0.05, OR > 1). Clustering resolved prognostic C1/C2 subtypes dependent on coordinated immunophenotypic programs. GPD1L knockdown promoted CRC cell proliferation. CONCLUSIONS: Genetic interrogation delineated causal immunome-CRC relationships at single-cell resolution. Immune-stratified CRC subtyping stratified patient outcomes. GPD1L exhibited tumor-suppressive functions. Our findings establish an integrated immunogenomic framework elucidating CRC pathogenesis with implications for precision immunotherapies.

Source: BMC Gastroenterology

DOI: 10.1186/s12876-025-03776-4

Authors: Ke-Jie He, Guoyu Gong

Institutions: Wenzhou Medical University, Quzhou City People's Hospital, Xiamen University

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190